Mutation in dna of bacteria and repairss

Chapter 13
Mutation, DNA Repair,…
© John Wiley & Sons, Inc.

Chapter Outline
Mutation: Source of the Genetic Variability Required for
Evolution
The Molecular Basis of Mutation
Mutation: Basic Features of the Process
Mutation: Phenotypic Effects
Assigning Mutations to Genes by the Complementation Test
Screening Chemicals for Mutagenicity: The Ames Test
DNA Repair Mechanisms
Inherited Human Diseases with Defects in DNA Repair
DNA Recombination Mechanisms

Mutation: Source of the Genetic
Variability Required for Evolution
Mutation
--A change in the genetic material (molecular level)
Mutant
--an organism that exhibits a novel phenotype

Types of Mutations
– Changes in chromosome number and
structure
– Point mutation--changes at specific
nucleotide in a gene (A,T,C,G)
• Substitution
• Duplication
• deletion
– Insertion mutations--insert fragment of DNA
– Deletion mutations--delete fragment of DNA

Mutation and Evolution
Mutation is the source of all genetic
variation (e.g.,chromatin remodeling).
Natural selection preserves the
combinations best adapted (or NOT) to
the existing environment.

Mutation: Basic Features of the Process
Mutations occur in all organisms from viruses to
humans.
They can occur spontaneously or be induced by
mutagenic agents.
Mutation is usually a random, non-adaptive process.

Mutation: Spontaneous or Induced
Spontaneous mutations occur without a
known cause due to unknown agents in the
environment.
Induced mutations result from exposure or
organisms to mutagens, physical and
chemical agents that cause changes in
DNA, such as ionizing irradiation, ultraviolet
light, or certain chemicals.

 Impossible to differentiate between spontaneous and induced mutations.
 Life can not exist with out solar light but
 UV ray of sunlight low energy cannot penetrate deep in tissues
 Solar light can cause mutations
– UV light of sun have low energy and
– Can penetrate Far in tissues and can be mutagenic to skin
 Xeroderma pigmentosa there can be sever cancer if exposed to sun light
 Many apparently spontaneous mutations are actually induced by mutagenic agents
 Mistakes in DNA replication 10-5
proof reading reduced upto 10-10
 Some mistakes may occur due to influence of genetic and environmental
 Spontaneous and induced mutations can not be distinguished at individual level but can be at population level
 Valid comparison by statistical methods
 Spontaneous mutation are infrequent
 Mutagenic agents can increase mutation frequency

Factors Influencing the Rate
of Spontaneous Mutations
Accuracy of the DNA replication
machinery
Efficiency of the mechanisms for the
repair of damaged DNA
Degree of exposure to mutagenic
agents in the environment

Mutation: Usually a Random, Non-
adaptive Process
Is mutation random (intrinsic) or directed by the
environment?
Replica plating was used to identify the presence
of antibiotic (chemical) resistant bacteria prior to
treatment with an antibiotic (chemicals).
Environmental stress does not cause mutations
but selects for mutants that are best adapted to the
environmental stress.

Results
The Colony that grow on the
strptomycine media and those that were
not grown were tested in liquid broth
subsequently tested for strptomycines
resistance
Those that form colonies on the selective
pate were found to contain resistant cells
Those that do not show resistance don
not show resistant cells

Phenotypic effect of mutation
 Mutations cause some detectable phenotypic change
 The effect ranges from being detected by specials genetic
procedures to modifications of morphology to lethals
 A gene is a specific sequence of nucleotide pairs coding for
specific poly peptide
 Mutation with in the gene thus will cause new alleles
 Because degeneracy of genetic code some base pair changes do
not change the protein products
 Genes containing mutations with small effects that can be
recognized only by special technique are called iso-alleles
 If mutations results in total loss of gene product activity the allele
are called lethal alleles
 Mutation may be recessive or dominant

Phenotypic effect of mutation
Morphological mutations
– Morph means “form.” Morphological mutations affect
the outwardly visible properties of an organism, such
as shape, color, or size. Albino ascospores
in Neurospora, curly wings in Drosophila, and dwarf
peas are all morphological mutations.
– Lethal mutations
• Conditional lethals

Conditional Lethal Mutants
Lethal in one environment (restrictive condition)
viable in second (permissive conditions)
Auxotrophs are unable to synthesize an essential
metabolite that is synthesized by prototrophs.
Auxotrophs can grow only when the essential
metabolite is supplied in the medium.
Temperature-sensitive mutants will grow at one
temperature but not at another.
Suppressor-sensitive mutants are viable only when
a second genetic factor, a suppressor, is present.

 Biochemical mutations
– Microbial cultures are convenient material for the study of biochemical mutations, which are identified by the loss or
change of some biochemical function of the cells. This change typically results in an inability to grow and proliferate
 Loss-of-function mutations
– Generally, loss-of-function (null) mutations are found to be recessive. In a wild-
type diploid cell, there are two wild-type alleles of a gene, both making normal gene product.
In heterozygotes (the crucial genotypes for testing dominance or recessiveness), the single
wild-type allele may be able to provide enough normal gene product to produce a wild-
type phenotype. In such cases, loss-of-function mutations are recessive. In some cases, the
cell is able to “upregulate” the level of activity of the single wild-type allele so that in
the heterozygote the total amount of wild-type gene product is more than half that found in the
homozygous wild type. However, some loss-of-function mutations are dominant. In such
cases, the single wild-type allele in the heterozygote cannot provide the amount of gene
product needed for the cells and the organism to be wild type.
 Gain-of-function mutations
– Because mutation events introduce random genetic changes, most of the time they result in
loss of function. The mutation events are like bullets being fired at a complex machine; most
of the time they will inactivate it. However, it is conceivable that in rare cases a bullet will
strike the machine in such a way that it produces some new function. So it is with mutation
events; sometimes the random change by pure chance confers some new function on
the gene. In a heterozygote, the new function will be expressed, and therefore the gain-of-
function mutation most likely will act like a dominant allele and produce some kind of
new phenotype.

Mutation: Somatic or Germinal
Germinal mutations occur in germ-line
cells and will be transmitted through the
gametes to the progeny.
Somatic mutations occur in somatic
cells; the mutant phenotype will occur
only in the descendants of that cell and
will not be transmitted to the progeny.
puberty (10-14 years)

Somatic mutations
 E.g the delicious and navel orange were originally mosaics in somatic
tissues
 These changes are apparently seems spontaneous mutations in single
cells which may leads to the production of entire branch with mutant
character
 By vegetative propagation of the these parts leads to the generation entire
plant with the desired phenotype
 If dominant mutations occure in germ cells their effect can be seen in next
progeny
 If mutations are recessive their effect are masked by the dominant allele
 If mutation is in the gametes only single member of the progeny may be
effected
 But if the mutation is in the gonial cells several gametes may receive
mutant alleles

Setth Wright 1971 noticed male lamb
with short legs
He thought to have a flock so they
cannot jump the fenses
He used this lamb to breed 15 ewes
2/15 new born lambs were short leg
Short leg were bred together and a line
was developed
So the mutations were germinal that
leads to make new progeny

The Molecular Basis of Mutation
Mutations alter the nucleotide sequences of genes in
several ways,
--the substitution of one base pair for another.
(A for T)
--the deletion (or addition) of one or a few base pairs.
( AT…….GC)

Tautomeric Shifts:
--chemical fluctuations,
--conformation states (stable==========unstable)
A:T
C:G
.
Py
Pu
Watson and crick pointed out that
structure of bases is not static Hydrogen
atom can move from one position to the
other in purines and Pyrimidines

Tautomeric Shifts Affect Base-Pairing
C:T
T:G
.

Mutation Caused by Tautomeric Shifts

Base Substitutions
A transition replaces a pyrimidine with another
pyrimidine or a purine for another purine.
A transversion replaces a pyrimidine with a
purine or a purine with a pyrimidine.

Frameshift Mutations: alteration of
the open reading frame (ORF)

Mutation Frequency
Frameshift, transition, transversion mutations
are infrequent
– Bacteria and phage: 10–8
to 10–10
per nucleotide
pair per generation
– Eukaryotes: 10–7
to 10–9
per nucleotide pair per
generation
1/107 to
1/109
Silent mutation: UCU=Ser;
UCA, UCC, UCG = Ser

The Electromagnetic Spectrum
X-rays induce mutations through ionization.
(DNA ionization--radical anions and cations-- G.
+)
Ultraviolet light induces mutations through excitation.
Causes of mutations
1-Radiation Induced Mutations
 Electro magnetic spectrum having short wave
length and high energy than visible light (WL
>o.1 um) can be subdivided in to
 Ionizing (X, gamma , cosmic) O.1-1nm
 Non Ionizing radiations (UV)
 IRs Useful in medical diagnosis penetrate deep
in tissues

 rays collide with atoms and cause the release of electrons, creating
positively charged free radicals or ions.
 The ions, in turn, collide with other molecules and cause the release of
additional electrons
 The result is that a cone of ions is formed along the track of each high-
energy ray as it passes through living tissues
 This process of ionization is induced by machine-produced X rays,
protons, and neutrons,
 as well as by the alpha, beta, and gamma rays released by
radioactive isotopes such as 32P, 35S, and the uranium-238 used in
nuclear reactors.

Ultraviolet rays, having lower energy than ionizing radiations, penetrate only
– the surface layer of cells in higher plants and animals and
– do not cause ionizations.
Ultraviolet rays dissipate their energy to the atoms they encounter, raising
the electrons
– in the outer orbitals to higher energy levels, a state referred to as excitation.

Ionizing Radiation Causes Changes
in Chromosome Structure
Ionizing radiation breaks chromosomes
and can cause deletions, duplications,
inversions, and translocations

Induced Mutations
Induced mutations occur upon exposure to
physical (energy) or chemical (reaction) mutagens.
Muller demonstrated that exposing Drosophila
sperm to X-rays increased the mutation
frequency.
Hermann J. Muller and Edgar Alternburg
measured the frequency (>150 fold increase) of
X-linked recessive lethal mutations in Drosophila.

C: crossover suppressor
l: recessive lethal mutation
B: bar-eye mutation
All progeny female
Male died
By using this
technoque muller
was able to
demonstrate an
increase in mutation
rate of upto 150 folds
after x ray treatment

Stability of carbon-containing molecules

Mutagenesis by Ultraviolet Irradiation
Hydrolysis of cytosine to
a hydrate may cause
mis-pairing during
replication
Cross-linking of adjacent
thymine forms
thymidine dimers,
which block DNA
replication and activate
DNA repair mechanisms.

UV-A 320 to 400 nm
UV-B/C <300 nm

Types of Chemical Mutagens
Chemicals that are mutagenic to both
replicating and non-replicating DNA
(e.g., alkylating agents and nitrous acid)
Chemicals that are mutagenic only to
replicating DNA (e.g., base analogs
and acridine dyes)

Chemical Mutagens

Alkylating Agents
 chemicals that donate alkyl groups to other molecules.
 induce transitions, transversions, frameshifts, and chromosome
aberrations (anomaly).
 Alkylating agents of bases can change base-pairing properties.
(GC to AT)
 can also activate errors during repair processes.

A Base Analog: 5-Bromouracil
--similar structures
--incorporated into DNA
--increase frequency of mis-pairing

Mutagenic Effects
of 5-Bromouracil

Nitrous Acid Causes Oxidative Deamination
of Bases
•HNO2 act directly on replicating and
non replicating DNA by oxidative
deamination
•Bases that contain amino group
convert them to keto group
•A, G, C
•Amino ----- keto change the bonding
potential
•A----converted to----hypoxanthene –pair
with cytocine
•C-----U------ pair with A
•G---xanthene ---pair with C like G

Intercalation of an Acridine Dye
Causes Frameshift Mutations
--(+) charges molecules
--Incorporated into DNA
--DNA is more rigid
--Change conformation
(non-bending)
ICR compounds have acridine moities
These are alkylating agents
The positively charged acridines intercalate, or
sandwich themselves, between the stacked base pairs
in DNA
DNA bases change confirmation of DNA Helix
Cause kinks
Which may lead to additions or deletions
Result in altered reading frames for the portion of the
gene distal to the mutation
Thus, acridine-induced mutations in exons of genes
usually result in nonfunctional gene products.

Hydroxylamine
(NH2OH)
Hydroxylamine is a hydroxylating (OH) agent.
Hydroxylamine (NH2OH) has a specific
mutagenic effect
Hydroxylamine hydroxylates the amino group
of cytosine and leads to G:C A:T transitions.
The resulting hydroxylaminocytosine base-
pairs with adenine, (leading to G:C → A:T transitions).
.

Because of its specificity, hydroxylamine has
been very useful in classifying transition
mutations
Mutations that are induced to revert to wild-type by nitrous
acid or base analogs, and therefore were originally
caused by transitions, can be divided into two classes on
the basis of their revertibility with hydroxylamine.
– (1) Those with an A:T base pair at the mutant site will not be
induced to revert by hydroxylamine.
– (2) Those with a G:C base pair at the mutant site will be induced
to revert by hydroxylamine.
Thus, hydroxylamine can be used to determine whether a
particular mutation was an A:T → G:C or a G:C → A:T
transition.

Mutations Induced by Transposons
(Repeats)
Fragmets/segments of DNA that are capable to shift / translocate/move from one location to another

Expansion of Trinucleotide Repeats
Simple tandem repeats are repeated
sequence of one to six nucleotide pairs (CGG,
CAG and CTG).
Trinucleotide repeats can increase in copy
number and cause inherited diseases (Fragile
X Syndrome, Huntington disease,
Spinocerebellar ataxia)

Expansion of Trinucleotide Repeats
 Repeated sequences of one to six nucleotide pairs are known as
simple tandem repeats
 Such repeats are dispersed throughout the human genome
 Repeats of three nucleotide pairs, trinucleotide repeats, can increase
in copy number and cause inherited diseases in humans.
 Several trinucleotides have been shown to undergo such increases in
copy number
 Expanded CGG trinucleotide repeats at the FRAXA site on the X
chromosome are responsible for fragile X syndrome
– the second most common form of inherited mental retardation in humans Normal X
chromosomes contain from 6 to about 50 copies of the CGG repeat at the FRAXA site.
– Mutant X chromosomes contain up to 1000 copies of the tandem CGG repeat at this
site (see Focus on Fragile X Syndrome and Expanded Trinucleotide Repeats in
Chapter 16).

• Mutations are induced by
• chemicals,
• ionizing irradiation,
• ultraviolet light, and
• endo(exo)genous transposable genetic elements.
• Point mutations are of three types:
(1) Transitions—purine for purine and pyrimidine for pyrimidine substitutions,
(2) Transversions—purine for pyrimidine and pyrimidine for purine substitutions,
and
(3) Frameshift mutations—additions or deletions of one or two nucleotide pairs,
which alter the reading frame of the gene distal to the site of the mutation.
Chromatin remodeling==Epigenetics
Summary

Forward Mutation
 The mutation of a wild-type gene to a form that results in a mutant
phenotype is referred to as forward mutation.
 However, sometimes the designation of the wild-type and mutant
phenotypes is quite arbitrary
 They may simply represent two different, but normal, phenotypes
 For example, geneticists consider the alleles for brown and blue
eye color in humans both to be wild-type
 However, in a population composed almost entirely of brown-eyed
individuals, the allele for blue eyes might be thought of as a mutant
allele

Mutation: A Reversible Process
Forward mutation—mutation of a wild-
type allele to a mutant allele.
Reverse mutation (reversion)—a
second mutation that restores the
original phenotype.
– Back mutation—a second mutation at the
same site.
– Suppressor mutation—a second mutation
at a different location in the genome.

Phenotype is not suppressed
Phenotype is restored

Mutation: Phenotypic
Effects
The effects of mutations on
phenotype range from no
observable change to lethality.
DNA/RNA/ polypeptide

Types of Mutations
Isoalleles have no effect on phenotype or small
effects that can be recognized only by special
techniques.
Null alleles result in no gene product or totally non-
functional gene products.
Recessive (Dominant) lethal mutations affect genes
required for growth of the organisms and are lethal in
the homozygous state.

X-linked Recessive Lethal
Mutations Alter the Sex Ratio
Monoploid: (Recessive or Dominant) positive mutational effect (phenotype)
Diploid: (Recessive)--positive mutational effect (phenotype)--homozygous
X-linked .....hemizygous

Recessive Mutations Often
Block Metabolic Pathways
(Recessive) lethal
mutations
Neutral mutations ( no effect on phenotype)

Expression of Wild-type and
Mutant Alleles

Mutations in Human Globin Genes
Adult hemoglobin (Hemoglobin A) contains two 
chains and two  chains.
Hemoglobin in patients with sickle-cell anemia
(Hemoglobin S) differs from Hemoglobin A at only
one position.
The sixth amino acid in the  chain is glutamic acid
in Hemoglobin A (HBBA
) and is valine in
Hemoglobin S (HBBS
). This substitution is caused
by mutation of a single base pair (T:A substitution).

Tay-Sachs Disease
Tay-Sachs disease
is an autosomal
recessive disease.
The mutation
causing Tay-Sachs
disease is in the
gene encoding
hexosaminidase A.
not linked to sex chromosome

Conditional Lethal Mutations
(Experimental)
Conditional lethal mutations are
– Lethal in the restrictive condition but
– Viable in the permissive condition.
Mutants with conditional lethal alleles can be
propagated under the permissive condition,
and the phenotype can be studied under
restrictive condition.

Conditional Lethal Mutants
Auxotrophs are unable to synthesize an
essential metabolite that is synthesized by
prototrophs. Auxotrophs can grow only when
the essential metabolite is supplied in the
medium.
Temperature-sensitive mutants will grow at
one temperature but not at another.
Suppressor-sensitive mutants are viable
only when a second genetic factor, a
suppressor, is present.

Morphogenesis in
Bacteriophage T4
This pathway was identified using mutants, electron
microscopy, and biochemistry.
Temperature-sensitive and suppressor-sensitive
# =gene

http://www.endocytosis.org/Dynamin/Shibire.html

Assigning Mutations to genes
by the Complementation test
The complementation or trans
test can be used to determine
whether two mutations are located
in the same chromosome or in two
different chromosomes.
Genetic tool to demonstrate: One gene....One polypeptide

Complementation test
 Scientist had no genetic tool to use in determining whether two mutations were in the
same or different genes
 This deficiency was resolved in the 1940s when Edward Lewis developed the
complementation test for functional allelism
 Before we discuss Lewis’s work, we need to define some new Terms
 A double heterozygote,
– which carries two mutations and their wild-type alleles, that is, m1 and m1 along with m2 and m2 , can
exist in either of two arrangements
 coupling or cis configuration
– When the two mutations are on the same chromosome, the arrangement is called the
coupling or cis configuration, and a heterozygote with this genotype is
called a cis heterozygote ( Figure 13.21a).
 repulsion or trans configuration.
– When the two mutations are on different chromosomes, the arrangement is called the repulsion or
trans configuration. An organism with this genotype is a trans heterozygote
( Figure 13.21b).

Assigning Mutations
Double heterozygote:
Two mutations (m1 and m2)
Wild-type (m1+ and m2+)
Co-exists in one or two
chromosomes
coupling
repulsion
Arrangement (organized)

1. In the 1940s and 1950s, Lewis observed that fruit flies carrying certain mutants inthe cis and
trans configurations had different phenotypes.
2. We will examine his results with two recessive eye color mutations white (w) and apricot (apr).
3. Flies that are homozygous for the X-linked mutations apr and w have apricot-colored eyes and
white eyes, respectively, in contrast to the red eyes of wild-type Drosophila.
4. When Lewis produced cis heterozygotes with the genotype apr w/apr+ w+, they had red eyes
just like wildtype flies (_ Figure 13.22a).
5. When he constructed trans heterozygotes with genotype apr w+/apr+ w, they had light apricot-
colored eyes (_ Figure 13.22b).
6. Both genotypes contained the same mutant and wild-type genetic information but in different
arrangements.
7. When organisms that contain the same genetic markers, but in different arrangements, have
different phenotypes, the markers are said to exhibit position effects.
8. The type of position effect that Lewis observed is called a cis-trans position effect.
9. Lewis’s discovery of cis-trans position effects led to the development of the complementation
test or trans test for functional allelism

Apr and W are
recessive mutations
X-linked mutations

The mutations must be tested pairwise by determining
the phenotypes of trans heterozygotes. That is, trans
heterozygotes must be constructed for each pair of
mutations and examined to determine whether they have
mutant or wild-type phenotypes.
Ideally, the complementation or trans test should be done
in conjunction with the cis test—a control that is often
omitted. Cis tests are performed by constructing cis
heterozygotes with each pair of mutations being studied
and determining whether the heterozygotes have mutant or
wild-type phenotypes. Together, the complementation or
trans test and the cis test are referred to as the cis-trans
test.

1. When the two mutations present in a trans heterozygote
are both in the same gene, both chromosomes will carry
defective copies of that gene.
• As a result, the trans heterozygote will contain only
nonfunctional products of the gene involved and will
have a mutant phenotype.
2. When a trans heterozygote has the wild-type phenotype,
the two mutations are said to exhibit complementation or
to complement each other and are located in different
genes.
• In this case, the trans heterozygote will contain
functional products of both genes and, therefore, will
exhibit the wild-type phenotype.

(head) (tail)

Screening Chemicals for mutagenicity:
The Ames test
The Ames test provides a simple and inexpensive method for
detecting the mutagenicity of chemicals (Carcinogens)
-intracellular
-extracellular
-enviromental
Auxotrophic prototrophic

DNA Repair Mechanisms
Living organisms contain many
enzymes that scan their DNA for
damage and initiate repair
processes when damage is
detected.

DNA Repair Mechanisms in E. coli
Light-dependent repair (photo-reactivation).
Excision repair.
Mismatch repair.
Post-replication repair.
Error-prone repair system (SOS response).

UV Light-
Dependent Repair:
Photolyase
Cleaves Thymine
Dimers.
--No endonuclease
--No Poly
--No ligase

Photolyase will bind to thymine dimers in DNA in the
dark, but it cannot catalyze cleavage of the bonds
joining the thymine moieties without energy derived from
visible light, specifically light within the blue region of the
spectrum. Photolyase also splits cytosine dimers and
cytosine-thymine dimers. Thus, when ultraviolet light is
used to induce mutations in bacteria, the irradiated cells
are grown in the dark for a
few generations to maximize the mutation frequency.z
Light-dependent repair or photoreactivation of DNA in
bacteria is carried out by a lightactivated enzyme called
DNA photolyase
When DNA is exposed to ultraviolet light, thymine dimers are
produced by covalent cross-linkages between adjacent thymine
residues
DNA photolyase recognizes and
binds to thymine dimers in DNA, and
uses light energy to cleave the
covalent cross-links

Excision Repair (steps)
A DNA repair endonuclease or endonuclease-
containing complex recognizes, binds to, and
excised the damaged base or bases.
A DNA Polymerase fills in the gap, using the
undamaged complementary strand of DNA as a
template.
DNA ligase seals the break left by DNA
polymerase.

Types of Excision Repair
Base excision repair pathways
remove abnormal or chemically
modified bases.
Nucleotide excision repair pathways
remove larger defects, such as thymine
dimers.

Base Excision Repair
AP:apyrimidinic site

( )

Nucleotide Excision Repair

Mismatch Repair in E. coli
Mismatching or mispairing of G and T
(DNA polymerase/exonuclease proofreading activity)
The A in GATC sequences is methylated subsequent to DNA
replication.
In newly replicated DNA, the parental strand is methylated, but
the new strand is not. This difference allows the mismatch repair
system to distinguish the new strand from the old strand.
The mismatched nucleotide is excised from the new strand and
replaced with the correct nucleotide, using the methylated
parental strand as a template.

Mismatch Repair in E. coli
MutS recognizes mismatches and binds to
them to initiate the repair process.
MutH and MutL join the complex.
MutH cleaves the unmethylated strand at
hemimethylated GATC sequences on either
side of the mismatch.
Excision requires MutS, MutL, MutU (DNA
helicase II), and an exonuclease.
DNA polymerase III fills in the gap, and DNA
ligase seals the nick.
Me
Me
Me
Me

Post-replication Repair in E. coli
A thymine dimer in the template strand blocks replication
(DNA Polymerase III does not recognize thymidine dimer)
DNA Polymerase III restarts DNA synthesis past the dimer,
leaving a gap in the nascent strand.
RecA binds to the single strand of DNA at the gap and
mediates base pairing with the homologous segment of the
sister double helix to fill the gap.
DNA polymerase fills the gap in the sister double helix, and
DNA ligase seals the nick.

The SOS Response in E. coli
 If DNA is heavily damaged by mutagenic agents, the
SOS response, which involves many DNA
recombination, DNA repair, and DNA replication
proteins, is activated.
 DNA dependent DNA Polymerase V replicates DNA
in damaged regions, but sequences in damaged
regions cannot be replicated accurately.
 This error-prone system eliminates gaps but increases
the frequency of replication errors (Pol II, IV and V are
low-fidelity polymerases)

Induction of the SOS Response
Error-prone repair system
In the absence of DNA damage, LexA binds to DNA
regions that regulate transcription of SOS response
genes and keeps their expression levels low.
When extensive DNA damage occurs, RecA binds to
single-stranded regions of DNA in damaged regions.
This activates RecA, which stimulates LexA to
inactivate itself. When LexA is inactivated, the SOS
response genes are expressed.

Inherited Human Diseases
with Defects in DNA Repair
Several inherited human disorders
result from defects in DNA repair
pathways.

Xeroderma Pigmentosum (XP)
Individuals with XP are
sensitive to sunlight (UV light).
The cells of individuals with XP
are deficient in the repair of
UV-induced damage to DNA.
Individuals with XP may
develop skin cancer or
neurological abnormalities.

DNA Recombination Mechanisms
Recombination between homologous
DNA molecules involves the activity of
numerous enzymes that
1-cleave,
2-unwind,
3-stimulate single-strand invasions of
double helices (RecA proteins),
4-repair, and
5-join strands of DNA.

Recombination
 In eukaryotes, crossing over is associated with the
formation of the synaptonemal complex during
prophase of meiosis I (Chiasmata).
 Crossing over involves the breakage of parental
chromosomes and rejoining of the parts in new
combinations.
 The Holliday model and the double-strand break
model are two explanations of the molecular basis of
recombination.

The Holliday Model: single strand break model

The Holliday Model: single strand break model
--DNA-dependent ATPase.
--can hold a single strand and
double strand together.
--DNA synapsis reaction
between a DNA double helix and a
homologous region of single
stranded DNA.
--catalyzes branch migration begins.

Mutation in dna of bacteria and repairss

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Mutation in dna of bacteria and repairss